My research is primarily involved in the development, prevention and treatment of type 1 (insulin-dependent or juvenile-onset) diabetes.

I am an investigator in several multicenter clinical trials involved in preventing type 1 diabetes. In addition, I collaborate with basic-science researchers from the BC Research Institute and from the The Centre of Human Islet Transplant and Beta Cell Regeneration at VGH, helping provide clinical material (most commonly, blood samples) for their research.

I also maintain our Division's large website providing resources for families of children with diabetes and other endocrine disorders, and for the professionals caring for these patients.

Most recently, working with local and provincial resources, I have helped initiate an endocrine treatment program for transgendered youth.


Glucose control and autonomic response during acute stress in youth with type 1 diabetes: A pilot study.
Pediatric diabetes
Guan L and Metzger DL and Lavoie PM and Collet JP
DOI: 10.1111/pedi.12680
PubMed: 29654713

WHO height charts can be safely substituted when calculating BP Z-scores in a North American clinic setting.
Paediatrics & child health
Rodd CJ and Metzger DL and Sharma AK
DOI: 10.1093/pch/pxx185
PubMed: 29769802

Adherence to a pediatric diabetic ketoacidosis protocol in children presenting to a tertiary care hospital.
Pediatric diabetes
DOI: 10.1111/pedi.12556
PubMed: 28664545

Hypogonadotropic Hypogonadism in Males with Glycogen Storage Disease Type 1.
JIMD reports
DOI: 10.1007/8904_2016_38
PubMed: 28160246

Exome Sequencing and the Management of Neurometabolic Disorders.
The New England journal of medicine
DOI: 10.1056/nejmoa1515792
PubMed: 27276562

Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects.
Endocrine-related cancer
DOI: 10.1530/erc-16-0082
PubMed: 26935837

LMS tables for waist-circumference and waist-height ratio Z-scores in children aged 5-19 y in NHANES III: association with cardio-metabolic risks.
Pediatric research
DOI: 10.1038/pr.2015.160
PubMed: 26331767

X-linked acrogigantism syndrome: clinical profile and therapeutic responses.
Endocrine-related cancer
DOI: 10.1530/erc-15-0038
PubMed: 25712922

Use of growth charts in Canada: A National Canadian Paediatric Surveillance Program survey.
Paediatrics & child health
DOI: 10.1093/pch/20.4.185
PubMed: 26038634

Managing type 1 diabetes in school: Recommendations for policy and practice.
Paediatrics & child health
PubMed: 25722642

Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation.
The New England journal of medicine
DOI: 10.1056/nejmoa1408028
PubMed: 25470569

Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization.
The Journal of clinical endocrinology and metabolism
DOI: 10.1210/jc.2014-1029
PubMed: 24823460

Hydrolyzed infant formula and early ß-cell autoimmunity: a randomized clinical trial.
DOI: 10.1001/jama.2014.5610
PubMed: 24915259

Clinical management of youth with gender dysphoria in Vancouver.
The Journal of pediatrics
DOI: 10.1016/j.jpeds.2013.10.068
PubMed: 24315505

Provincial disparities of growth hormone coverage for young adult survivors of paediatric brain tumours across Canada.
Healthcare Policy
PubMed: 24726076

B7-H4 expression in normal and diseased human islet ß cells.
DOI: 10.1097/mpa.0b013e31829695d2
PubMed: 24326367

Extending World Health Organization weight-for-age reference curves to older children.
BMC pediatrics
DOI: 10.1186/1471-2431-14-32
PubMed: 24490896

Canadian endocrinologists’ views on growth hormone replacement therapy in adult survivors of pediatric brain tumours following achievement of final height
BC Medical Journal

Canadian Pediatric Endocrine Group extension to WHO growth charts: Why bother?
Paediatrics & child health
PubMed: 24421695

Case 2: Pimples in prepuberty: A five-year-old with an unusual cause of facial comedones.
Paediatrics & child health
DOI: 10.1093/pch/18.2.91a
PubMed: 24421664

Endogenous expression of B7-H4 improves long-term murine islet allograft survival.
DOI: 10.1097/tp.0b013e318277229d
PubMed: 23192157

Occurrence of slipped capital femoral epiphysis in children undergoing gonadotropin-releasing hormone agonist therapy for the treatment of central precocious puberty.
Hormone research in paediatrics
DOI: 10.1159/000351028
PubMed: 23859950

When genetic load does not correlate with phenotypic spectrum: lessons from the GnRH receptor (GNRHR).
The Journal of clinical endocrinology and metabolism
DOI: 10.1210/jc.2012-1264
PubMed: 22745237

Blockade of both B7-H4 and CTLA-4 co-signaling pathways enhances mouse islet allograft survival.
DOI: 10.4161/isl.21239
PubMed: 22878670

B7-H4 induces donor-specific tolerance in mouse islet allografts.
Cell transplantation
DOI: 10.3727/096368912x633815
PubMed: 21929869

B7-H4 Treatment of T Cells Inhibits ERK, JNK, p38, and AKT Activation.
PloS one
DOI: 10.1371/journal.pone.0028232
PubMed: 22238573

Generation of transplantable Beta cells for patient-specific cell therapy.
International Journal of Endocrinology
DOI: 10.1155/2012/414812
PubMed: 22611393

Early treatment of NOD mice with B7-H4 reduces the incidence of autoimmune diabetes.
DOI: 10.2337/db11-0375
PubMed: 21984581

Novel use of F-DOPA PET/CT imaging in a child with paraganglioma/pheochromocytoma syndrome.
Pediatric radiology
DOI: 10.1007/s00247-011-2109-0
PubMed: 21567141

Validation of diabetes case definitions using administrative claims data.
Diabetic medicine : a journal of the British Diabetic Association
DOI: 10.1111/j.1464-5491.2011.03238.x
PubMed: 21392063

B7-H4 Pathway in Islet Transplantation and ß-Cell Replacement Therapies.
Journal of transplantation
DOI: 10.1155/2011/418902
PubMed: 22028949

Early treatment of NOD mice with B7-H4 reduces the incidence of autoimmune diabetes

Methylation profiling in individuals with Russell-Silver syndrome.
American journal of medical genetics. Part A
DOI: 10.1002/ajmg.a.33204
PubMed: 20082469

Diabetic ketoacidosis in children and adolescents: an update and revised treatment protocol
BC Medical Journal

Local expression of B7-H4 by recombinant adenovirus transduction in mouse islets prolongs allograft survival.
DOI: 10.1097/tp.0b013e318195e5fa
PubMed: 19307783

Twenty-one additional cases of familial renal glucosuria: absence of genetic heterogeneity, high prevalence of private mutations and further evidence of volume depletion.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
DOI: 10.1093/ndt/gfn386
PubMed: 18622023

Skewed X-chromosome inactivation is associated with primary but not secondary ovarian failure.
American journal of medical genetics. Part A
DOI: 10.1002/ajmg.a.31679
PubMed: 17431892

Autosomal dominant pseudohypoaldosteronism type 1: mechanisms, evidence for neonatal lethality, and phenotypic expression in adults.
Journal of the American Society of Nephrology : JASN
DOI: 10.1681/asn.2005111188
PubMed: 16611713

Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism.
Proceedings of the National Academy of Sciences of the United States of America
DOI: 10.1073/pnas.0600962103
PubMed: 16606836

Suppression of human T-cell responses to beta-cells by activation of B7-H4 pathway.
Cell transplantation
DOI: 10.3727/000000006783981837
PubMed: 28871868

Novel TRPM6 mutations in 21 families with primary hypomagnesemia and secondary hypocalcemia.
Journal of the American Society of Nephrology : JASN
DOI: 10.1681/asn.2004110989
PubMed: 16107578

Regulation of TNF-related apoptosis-inducing ligand-mediated death-signal pathway in human beta cells by Fas-associated death domain and nuclear factor kappaB.
Human immunology
DOI: 10.1016/j.humimm.2005.03.009
PubMed: 16112027

Autosomal dominant resistance to thyrotropin as a distinct entity in five multigenerational kindreds: clinical characterization and exclusion of candidate loci.
The Journal of clinical endocrinology and metabolism
DOI: 10.1210/jc.2005-0572
PubMed: 15870119

Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial--Type 1.
Diabetes care
DOI: 10.2337/diacare.28.5.1068
PubMed: 15855569

Synergistic inhibition of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human pancreatic beta cells by Bcl-2 and X-linked inhibitor of apoptosis.
Human immunology
DOI: 10.1016/j.humimm.2004.12.002
PubMed: 15784465

Tumor necrosis factor-related apoptosis-inducing ligand and CD56 expression in patients with type 1 diabetes mellitus.
DOI: 10.1097/01.mpa.0000148515.77497.4b
PubMed: 15714132

Oculorespiratory syndrome after influenza immunization in children.
The Pediatric infectious disease journal
DOI: 10.1097/01.inf.0000148924.89558.d5
PubMed: 15665712

Long on QT and low on calcium.
Cardiology in the young
DOI: 10.1017/s1047951104006134
PubMed: 15680004

Spectrum of HNF1A and GCK mutations in Canadian families with maturity-onset diabetes of the young (MODY).
Clinical and investigative medicine. Medecine clinique et experimentale
PubMed: 15305805

Addison’s disease in a child with systemic lupus erythematosus
Pediatric Rheumatology Online Journal

Current approaches to the prevention of type 1 diabetes
BC Medical Journal

Telephone contact by a diabetes nurse educator improves hemoglobin A1c in adolescents with poorly controlled type 1 diabetes: a randomized controlled trial
Canadian Journal of Diabetes

GCK and HNF1A mutations in Canadian families with maturity onset diabetes of the young (MODY).
Human mutation
DOI: 10.1002/humu.9090
PubMed: 12442280

TNF-related apoptosis-inducing ligand death pathway-mediated human beta-cell destruction.
DOI: 10.1007/s00125-002-0926-2
PubMed: 12488957

Effects of insulin in relatives of patients with type 1 diabetes mellitus.
The New England journal of medicine
DOI: 10.1056/nejmoa012350
PubMed: 12037147

beta-cell antigen-specific CD56(+) NKT cells from type 1 diabetic patients: autoaggressive effector T cells damage human CD56(+) beta cells by HLA-restricted and non-HLA-restricted pathways.
Human immunology
DOI: 10.1016/s0198-8859(02)00372-5
PubMed: 12039407

Nine novel mutations in NR0B1 (DAX1) causing adrenal hypoplasia congenita.
Human mutation
DOI: 10.1002/humu.1236
PubMed: 11748852

Spectrum of mutations of the AAAS gene in Allgrove syndrome: lack of mutations in six kindreds with isolated resistance to corticotropin.
The Journal of clinical endocrinology and metabolism
DOI: 10.1210/jc.86.11.5433
PubMed: 11701718

High prevalence of celiac disease in patients with type 1 diabetes detected by antibodies to endomysium and tissue transglutaminase.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie
DOI: 10.1155/2001/640796
PubMed: 11381296

Increased prevalence of celiac disease in girls with Turner syndrome detected using antibodies to endomysium and tissue transglutaminase.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie
DOI: 10.1155/2000/172914
PubMed: 11125180

Cross-reactive rubella virus and glutamic acid decarboxylase (65 and 67) protein determinants recognised by T cells of patients with type I diabetes mellitus.
DOI: 10.1007/s001250051373
PubMed: 10907121

CD4+ and CD8+ T-cell clones from congenital rubella syndrome patients with IDDM recognize overlapping GAD65 protein epitopes. Implications for HLA class I and II allelic linkage to disease susceptibility.
Human immunology
DOI: 10.1016/s0198-8859(99)00037-3
PubMed: 10439311

Sex-Steroid—Hormone Modulation of the Somatotropic Axis During Normal Male Puberty
Sex-Steroid Interactions with Growth Hormone
Daniel L. Metzger and James R. Kerrigan
DOI: 10.1007/978-1-4612-1546-2_4

Antenatal treatment for classic 21-hydroxylase forms of congenital adrenal hyperplasia and the issues.
Genetics in medicine : official journal of the American College of Medical Genetics
PubMed: 11256677

A provincial protocol for the treatment of diabetic ketoacidosis in children
BC Medical Journal

Estrogen and testosterone, but not a nonaromatizable androgen, direct network integration of the hypothalamo-somatotrope (growth hormone)-insulin-like growth factor I axis in the human: evidence from pubertal pathophysiology and sex-steroid hormone replacement.
The Journal of Clinical Endocrinology and Metabolism
DOI: 10.1210/jcem.82.10.4317
PubMed: 9329378

The short-term infusion of ovine corticotropin-releasing hormone does not alter luteinizing hormone concentrations in young adult men.
The Journal of Clinical Endocrinology and Metabolism
DOI: 10.1210/jcem.82.2.3782
PubMed: 9024279

Estrogen and diclofenac sodium therapy in a prepubertal female with idiopathic juvenile osteoporosis.
Journal of pediatric endocrinology & metabolism : JPEM
DOI: 10.1515/jpem.1995.8.2.135
PubMed: 7584708

Gonadal steroid hormone regulation of the somatotropic axis during puberty in humans Mechanisms of androgen and estrogen action.
Trends in endocrinology and metabolism: TEM
DOI: 10.1016/1043-2760(94)p3204-k
PubMed: 18407221

Estrogen receptor blockade with tamoxifen diminishes growth hormone secretion in boys: evidence for a stimulatory role of endogenous estrogens during male adolescence.
The Journal of clinical endocrinology and metabolism
DOI: 10.1210/jcem.79.2.8045971
PubMed: 8045971

Radiological case of the month. Case 2. Untreated chronic lymphocytic thyroiditis presenting as a pituitary mass and secondary hypocortisolism.
Archives of pediatrics & adolescent medicine
DOI: 10.1001/archpedi.1994.02170070059010
PubMed: 8019626

The hepatopulmonary syndrome masquerading as pulmonary Langerhans-cell histiocytosis. Hepatopulmonary Syndrome Study Group.
Annals of internal medicine
DOI: 10.7326/0003-4819-121-1-199407010-00006
PubMed: 8198345

Cholinergic and opioid involvement in release of growth hormone during exercise and recovery.
Journal of applied physiology (Bethesda, Md. : 1985)
PubMed: 8226493

Characterization of pulsatile secretion and clearance of plasma cortisol in premature and term neonates using deconvolution analysis.
The Journal of Clinical Endocrinology and Metabolism
DOI: 10.1210/jcem.77.2.8345052
PubMed: 8345052

Permanent neonatal diabetes mellitus and pancreatic exocrine insufficiency resulting from congenital pancreatic agenesis.
American journal of diseases of children (1960)
PubMed: 8506821

Alterations in the neuroendocrine control of growth hormone secretion in the uremic rat.
Kidney international
DOI: 10.1038/ki.1993.146
PubMed: 8099633

Androgen receptor blockade with flutamide enhances growth hormone secretion in late pubertal males: evidence for independent actions of estrogen and androgen.
The Journal of clinical endocrinology and metabolism
DOI: 10.1210/jcem.76.5.8496305
PubMed: 8496305


Current Project
I am currently involved in two multicenter trials involved with either the prevention or the early treatment of type 1 diabetes: the Diabetes TrialNet and the TRIGR (Trial to Reduce IDDM in the Genetically at Risk).

I also work closely with basic-science researchers at BCRI and at The Centre of Human Islet Transplant and Beta Cell Regeneration at VGH on an variety of studies related to the various immunological processes involved in the development of type 1 diabetes in humans.

Finally, I am a co-investigator in research evaluating a comprehensive provincial health care model for children with diabetes using existing population databases.

Honours & Awards

Outstanding Achievement Award, Canadian Diabetes Association — 2003

Family-Centred Care Award of Distinction, BCCH Partners in Care — 2003

The Noni MacDonald Award, Canadian Pediatric Society — 2014

Research Group Members

Karnjit Sarai, Volunteer